Drug Interactions with Digoxin

Abstract

Multiple drug administration may affect the actions of digoxin either by altering its myocardial effects (dose-response relationship or pharmacodynamic effect) or by altering the absorption, storage or excretion of the drug (a pharmacokinetic effect). The major pharmacodynamic interactions include potentiation of digitalis toxicity by potassium-wasting diuretics and by succinlycholine. β-Blocking drugs also increase the potential for digoxin to produce adverse sinus or A-V node dysfunction. The pharmacokinetic interactions can be divided into drug interactions which alter digoxin absorption and those which change renal excretion. Estimates of the former are usually based on either steady-state or single dose studies of bioavailability. These studies have demonstrated significant reduction of absorption of oral digoxin by simultaneously administered liquid antacids, cholestyramine, kaolin-pectin, and meals of high fibre content. Reduced digoxin absorption also occurs secondary to therapy with sulphasalazine, para-aminosalicylic acid, and neomycin, probably due to their effect upon gut wall function. Propantheline and diphenoxylate with atropine, which decrease gut motility, increase digoxin absorption, whereas metoclopramide, which increases motility, depresses absorption. The renal excretion of digoxin is not changed importantly by diuretics such as frusemide but is decreased by spironolactone, possibly due to inhibition of renal tubular secretion of digoxin. Quinidine produces dramatic persistent increases in digoxin serum levels, due to decreased renal clearance of the glycoside, without changing the glomerular filtration. In addition to this renal effect, quinidine also seems to decrease the volume of distribution of digoxin, which results in acutely altered digoxin levels even within the first day after quinidine administration. Alteration of the timing of the administration of digoxin from that of a second drug (e.g. as with liquid antacids, kaolin-pectin, or meals of high fibre content), or alteration of the dose of digoxin based on the anticipated change in kinetics (as with spironolactone, quinidine or medications altering gut function or motility), can improve clinical effectiveness of digoxin therapy. However, because of individual variation in the impact of these interactions, routine monitoring of digoxin serum levels is strongly recommended under such circumstances to enhance clinical efficacy and patient safety.